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Biomedical subjects

W E Connor

Publications and source records attributed to W E Connor.

At least 163 records · Page 9Linked to original sources
PubMed1981

High density lipoprotein metabolism in a patient with abetalipoproteninemia.

The concentration of individual plasma apoproteins together with the in vivo metabolism of 125I-labelled high density lipoprotein was studied in an adult male patient with abetalipoproteinemia. Plasma concentrations of cholesterol (26 mg/dl) and triglyceride (5 mg/dl) were markedly reduced and apoprotein B was absent. The concentrations of apo AI, apo AII, CI, CII, CIII and E were also lower than in normal subjects. To further evaluate these changes we studied the in vivo metabolism of autologous 125I-labelled HDL over a period of 13 days. The plasma half-life (4.1 days) and fractional catabolic rate (0.23) were similar to previously reported values for the normal subjects, but overall synthesis of apoproteins AI (5.7 mg/kg/day) and AII (3.6 mg/kg/day) were significantly reduced. After separation of delipidated HDL apoproteins by polyacrylamide-gel electrophoresis we were unable to demonstrate any difference in the half-life or fractional catabolic rates of apoproteins AI and AII and CII pulu CIII. We conclude that the low concentrations of apoproteins AI and AII in the plasma of our patient with abetalipoproteinemia are a consequence of reduced synthesis and do not reflect enhanced catabolism

Abetalipoproteinemia↗
PubMed1981

Cholesterol and bile acid balance in Macaca fascicularis. Effects of alfalfa saponins.

We determine the effects of alfalfa top saponins on cholesterol and bile acid balance in eight cynomolgus macaques (Macaca fascicularis). The monkeys ate semipurified food containing cholesterol with or without added saponins. The saponins decreased cholesterolemia without changing the levels of high density lipoprotein-cholesterol; hence, they reduced the total cholesterol/high density lipoprotein-cholesterol ratio. Furthermore, they decreased intestinal absorption of cholesterol, increased fecal excretion of endogenous and exogenous neutral steroids and bile acids, and decreased the percent distribution of fecal deoxycholic and lithocholic acids. The fecal excretion of fat was also slightly increased, but steatorrhea did not occur. We saw no signs of toxicity in the monkeys after 6 or 8 wk of saponin ingestion. The data suggest that alfalfa top saponins may be of use in the treatment of patients with hypercholesterolemia, but long-term studies on possible toxicity are needed before this therapy can be recommended for humans.

Animals↗
PubMed1981

Absorption and transport of shellfish sterols in human subjects.

While individually cholesterol is the most abundant sterol in clams, oysters, and scallops, five different major noncholesterol sterols (a C-26 sterol, 22-dehydrocholesterol, brassicasterol, 24-methylene cholesterol, and a C-29 sterol) comprise some 60% of the total sterols, a situation unique among foods of animal origin that humans consume. In order to measure the intestinal absorption and transport of these noncholesterol shellfish sterols by humans, clams, oysters, and scallops were fed daily for 3-4 wk to 9 subjects and in a single meal to 8 subjects. The major shellfish sterols in the diet and in the plasma, individual plasma lipoproteins, red blood cells, and feces were analyzed by digitonin precipitation, thin-layer and gas-liquid chromatography-mass spectrometry. The absorption of these shellfish sterols was ascertained both by their appearance in the blood of the subjects fed shellfish and by their intake and output in the feces. After daily feeding for 3--4 wk, shellfish sterols were identified for the first time in the plasma lipids, in lipoproteins (chiefly in low-density lipoprotein), and in red blood cells of all subjects. The absorption of the dietary C-26 sterol, 22-dehydrocholesterol, brassicasterol, 24-methylene cholesterol was 54%, 35%, 4% and 11%, respectively. Our data indicated that the intestinal mucosa of humans absorbs these unusual sterols, and then they enter into the tissues and overall sterol metabolism of the body.

Adult↗
PubMed1981

The biosynthesis, absorption, and origin of cholesterol and plant sterols in the Florida land crab.

In order to study the biosynthesis, composition, and origin of sterols in the Florida land crabs, Cardisoma guanhumi (Latreille), we fed 17 male crabs either a cholesterol-free or a high cholesterol diet for 2 to 7 weeks. The origin of sterols in these crabs, whether from biosynthesis or from the diet, was determined by tahree procedures: the incorporation of isotopic mevalonate into the cholesterol when the diet was cholesterol-free; the absorption of isotopic cholesterol and sitosterol from the diet; the cholesterol and plant sterol concentrations of hepatopancreas, plasma, and muscle under conditions of cholesterol-free and high cholesterol diets. In addition, the interconversion of cholesterol and sitosterol was investigated. Dietary sterols of plant and animal sources were readily absorbed and provided the major source of sterols for this species of crab. The biosynthesis of cholesterol from mevalonate in this crab was minimal. However, cholesterol was synthesized from dietary sitosterol by dealkylation. Cholesterol and the three plant sterols (24 epsilon-methyl cholesterol, stigmasterol, and sitosterol) were found in the hepatopancreas, plasma, and muscle of the crab. Plant sterols contributed from 9 to 37% of the total sterols in the hepatopancreas, plasma, and muscle of the crabs fed a cholesterol-free diet.

Absorption↗
PubMed1981

The effects of dietary omega 3 fatty acids on platelet composition and function in man: a prospective, controlled study.

The rarity of atherosclerotic vascular disease and a mild bruising tendency in Greenland Eskimos has been linked to their ingestion of omega 3 fatty acids contained in foods obtained from the sea. Previous studies have shown that feeding salmon oil to normal volunteers resulted in reductions of plasma cholesterol and triglycerides. We wished to learn whether salmon oil feeding would result in the incorporation of omega 3 fatty acids into platelets and whether platelet function or platelet-vessel interaction would be altered. Diets containing salmon oils led to the incorporation of eicosapentaenoic acid (C20:5 omega 3) into platelets (6.1%) with a reduction in arachidonic acid (C20:4 omega 6). The ratio of C20:5/C20:4 increased from 0.0045 on the control diet to 0.3 on the salmon diet. Bleeding times were prolonged (from 6.75 to 10 min, p less than 0.005), platelet retention on glass beads was mildly reduced (from 89% to 78%, p less than 0.0005), and platelet aggregation in response to dilute concentrations of ADP was inhibited in the subjects ingesting the salmon oil. We conclude that in normal subjects dietary omega 2 fatty acids derived from salmon oil are incorporated into platelet phospholipids and that these changes are accompanied by alterations in bleeding time and platelet function.

Adenosine Diphosphate↗
PubMed1980

Abetalipoproteinemia. Report of two cases and review of therapy.

The clinical presentation and course of abetalipoproteinemia in two male patients, a child and an adult, are described. Apoprotein B was absent in both cases and each patient had > 50% acanthocytes present on peripheral blood smear. Family studies revealed normal lipid profiles in the parents of both patients, which is consistent with the usual autosomal recessive inheritance of this disorder. In addition to a low-fat diet, both patients have been maintained on high doses of vitamins A and E. In the adult patient, detailed evaluations over a five-year period have failed to show any progression of neurological disease while maintained on high-dose vitamins. The role of supplemental vitamins A and E in the therapy of abetalipoprotenemia is discussed.

Abetalipoproteinemia↗
PubMed1980

Ectopic xanthomas in familial (type II) hypercholesterolemia.

Xanthomas ordinarily occur in the skin and tendons of patients with severe hyperlipidemia. These xanthomas include xanthelasma, tuberous xanthoma, tendon xanthoma and eruptive xanthoma. Two patients with hypercholesterolemia are now described with xanthomas found in other locations, one deep in the mediastinum and one in the muscles of the buttock. These masses simulated the occurrence of neoplastic tumors but on pathological and chemical examination proved to be typical xanthomata. Ectopic xanthomas should be considered in the differential diagnosis of masses in patients with familial hypercholesterolemia.

Aged↗
PubMed1980

The dietary prevention of coronary heart disease: dietary cholesterol and fat.

Epidemiological, laboratory and experimental studies make it clear that dietary cholesterol (DC) and saturated fat, independently and together, are hypercholesterolaemic and atherogenic. Some work suggests that DC, usually given as egg yolk, is the more important, but often they are consumed together. There is a threshold, usually between 100 and 200 mg/day, below which small increments do not affect plasma cholesterol (PC) and another, usually between 500 and 600 mg/day, above which there is little additional change. However, there is considerable individual variation. Recent work suggests that regression of atherosclerosis can occur in the human as in the non-human primate. An alternative, phased, preventive diet has been designed which is nutritionally adequate, ecologically sound, and economical. It also has an historical basis.

Animals↗
PubMed1980

The mass uptake of cholesterol ester from low density lipoproteins by cultured smooth muscle and adventitial cells of human aortas.

Cultured human smooth muscle and adventitial cells were incubated with human serum and low density lipoprotein (LDL) to study the uptake and accumulation of cholesterol ester from exogenous LDL. The cellular total cholesterol varied with the amount of LDL cholesterol in the medium. The cholesterol ester content increased 4-fold after 2 hours of incubation. A 6-fold rise occurred by 24 hours and continued to 72 hours. The cholesterol ester of the adventitial cells was markedly depleted by incubation with abetalipoproteinemic serum or with a lipid-depleted plasma fraction. By the use of 14C-labeled LDL free cholesterol in the incubation medium, we calculated that some 70-80% of the total accumulated cholesterol ester after 24 hours of incubation was derived from LDL cholesterol ester, and only 20-30% was synthesized by the cells. These studies demonstrated conclusively that human cells greatly increase their cholesterol ester mass after incubation with LDL.

Aorta↗
PubMed1980

Impaired cortisol secretion in abetalipoproteinemia.

In the adrenal gland cholesterol for steroid biosynthesis is derived from both de novo biosynthesis and receptor mediated uptake of plasma low density lipoproteins (LDL). In the present study we have compared ACTH stimulated adrenal production of cortisol in four control subjects and one adult male patient with abetalipoproteinemia, a disorder in which LDL is absent. Basal morning cortisol levels in the plasma in the control subjects (13.3 +/- 1.6 microgram/dl) and abetalipoproteinemic patient (14.6 micrograms/dl) were similar. During infusion of alpha 1, 24 ACTH however, plasma cortisol levels were higher in the control subjects than in the abetalipoproteinemic patient and this difference was significant at times after 4 hours. Urinary excretion of both 17-hydroxy and 17-ketosteroids over the 24 hour infusion period was also significantly lower in the abetalipoproteinemia patient indicating that cortisol production rates were reduced. Our results suggest that in the absence of plasma low density lipoproteins, as occurs in abetalipoproteinemia, the maximal production of adrenal corticosteroids is impaired. By inference, these findings lend in vivo support to the view that plasma low density lipoproteins serve as an important source of cholesterol for adrenal steroidogenesis in man.

17-Hydroxycorticosteroids↗
PubMed1980

A comparison of the turnover and metabolism cholesterol in normal and atherosclerotic monkey aortas.

Rhesus monkeys were fed high cholesterol and cholesterol-free diets for 21-24 months. The animals were then given isotopic cholesterol intravenously and autopsied from 1 to 51 weeks later. The plasma and aortic cholesterol contents were 633 +/- 130 mg/dl and 35.6 +/- 11.4 mg/g dried tissue (45.5% in ester form) for atherosclerotic monkeys and 135 +/- 25 mg/dl and 9.9 +/- 3.6 mg/g (15.0% in ester form) for control monkeys, respectively. The minimal influx rate of cholesterol from plasma into the aorta was much greater for atherosclerotic animals, 0.470 +/- 0.20 mg/g per day versus 0.088 +/- 0.031 for control monkeys. There was a rapid turnover of both free and esterified cholesterol in the atherosclerotic aortas, greater than for normal aortas. These studies of cholesteryl ester metabolism indicated a likely origin of aortic cholesteryl ester from the plasma cholesteryl esters. Our data indicated a dynamic cholesterol metabolism and turnover in the aorta during atherogenesis.

Animals↗
PubMed1980

Lipid metabolism in abetalipoproteinemia: a study of cholesterol absorption and sterol balance in two patients.

The concept that an absence of apoprotein B in plasma may result in increased cholesterol biosynthesis was investigated by sterol balance techniques in 2 male patients with abetalipoproteinemia, one an adult, the other a child. Total body synthesis of cholesterol in both the adult patient (19.3 +/- 3.8 mg/kg/day vs. 10.8 +/- 0.9 mg/kg/day in controls) and the child with abetalipoproteinemia (34.9 mg/kg/day vs. 14.5 +/- 3.8 mg/kg/day in control children) was significantly higher than in controls whereas bile acid synthesis was similar in both groups. Absorption of orally administered [1,2-3H]cholesterol was lower in the abetalipoproteinemic subjects than the controls and subsequent labeling of plasma cholesterol in the former patients was minimal (less than 3% of controls). The mechanisms for the increased sterol synthesis in abetalipoproteinemia may relate to the absence of chylomicrons and low density lipoproteins in plasma, but the magnitude of the increase can be largely explained on the basis of enhanced sterol losses that occur secondary to malabsorption of biliary cholesterol.

Abetalipoproteinemia↗
PubMed1980

Sterols of human gallstones: the recent identification of eight different digitonin precipitable sterols.

In this study, we report for the first time the presence of many noncholesterol sterols in human gallstones. Gallstones were obtained from 17 patients at cholesystectomy. They were rich in sterol composition, some 52.8% by weight. A number of different sterols were found: 22-dehydrocholesterol 0.29% of total sterols; cholestanol, 1.54%; lathosterol, 1.92%; 24-methylene cholesterol and campesterol, 0.64%; stigmasterol, 0.02%; beta-sitosterol, 0.21%; and cholesterol, 95.33%. These individual sterols were identified by a variety of methods which included final verification by combined gas chromatography-mass spectroscopy. These unusual sterols were derived either from the diet or from the metabolism of cholesterol in the body. Their presence might well affect the lithogenicity of the bile and raises questions about their metabolism and function generally in the body.

Cholelithiasis↗
PubMed1980

The long term effects of dietary cholesterol upon the plasma lipids, lipoproteins, cholesterol absorption, and the sterol balance in man: the demonstration of feedback inhibition of cholesterol biosynthesis and increased bile acid excretion.

In order to study the metabolic responses of humans consuming a diet moderately high in cholesterol content, we carried out a long-term sterol balance study, up to 25 weeks in duration. Two subjects, one normocholesterolemic and one hypercholesterolemic, were given, in sequence, a very low cholesterol diet and then a diet containing 1000 mg cholesterol per day. The plasma lipids, lipoproteins, cholesterol absorption and synthesis, and fecal steroid excretion were then measured during the different dietary periods (10-14 weeks of a very low cholesterol diet and 11 weeks of a moderately high cholesterol diet). During the high cholestrol dietary period, the plasma cholesterol level increased from 280 to 427 mg/dl for Subject 1 and from 123 to 166 mg/dl for Subject 2. The low density lipoprotein (LDL) cholesterol increased from 215 to 318 mg/dl and from 76 to 112 mg/dl. The high density lipoprotein (HDL) cholesterol also increased. Of the possible compensatory mechanisms against cholesterol overloading from the diet, two mechanisms were partially effective: cholesterol biosynthesis decreased (feedback inhibition) and bile acid excretion increased. Cholesterol absorption remained unchanged after the high cholesterol diet and was not a compensatory mechanism despite earlier assumptions that it might be. In spite of these compensatory mechanisms, the cholesterol feeding led to a 44% increase in the plasma cholesterol levels of these subjects. The predominant component of the plasma cholesterol increase was in the cholesterol transported by LDL and with presumably greater atherogenicity as a result. In the hypercholesterolemic subject, the LDL/HDL ratio increased and there was a net storage of cholesterol in the body. Storage of cholesterol did not occur in the normal subject.

Adult↗
PubMed1979

Sterol balance in abetalipoproteinemia: studies in a patient with homozygous familial hypobetalipoproteinemia.

A new case of homozygous familial hypobetalipoproteinemia is reported in a 16-yr-old girl. Apoprotein B was absent from plasma and the patient had acanthocytes and steatorrhea, but minimal neurologic dysfunction. Total body cholesterol synthesis was assessed intermittently over a 30-mo period by sterol balance techniques. The rate of synthesis of cholesterol was higher (15.0 +/- 2.9 mg/kg/day) in the patient (8.3 +/- 0.4 mg/kg/day than in 3 control children, p less than 0.005). Bile acid synthesis was similar (4.6 +/- 1.8 versus 4.0 +/- 1.7 mg/kg/day) in the patient and controls, but total body sterol synthesis was significantly higher (19.6 +/- 3.0 versus 12.2 +/- 2.0, p less than 0.005). The absorption of orally administered [1,2,(3)H] cholesterol in the patient was low and less than 0.5% of the label appeared in the total plasma volume at all times up to 48 hr. Estimates of the extent that malabsorption of biliary cholesterol contributes to the enhanced excretion of neutral sterols in this case indicate that all of the increase can be explained on this basis. Thus, although the mechanisms for the increased sterol synthesis in this case may relate to the absence of chylomicrons and low density lipoproteins in plasma, the magnitude of the increase can be fully explained on the basis of a compensatory mechanism to maintain cholesterol homeostasis in the face of enhanced fecal losses.

Abetalipoproteinemia↗
PubMed1979

The food and nutrient intakes of the Tarahumara Indians of Mexico.

A nutritional survey of 372 semiacculturated Tarahumara Indians in the Sierra Madre Occidental Mountains of Mexico was carried out to determine the composition of their diet and its nutritional adequacy. Dietary histories from 174 adults and 198 children were obtained by interviews and field observations during 1973 and 1974. The histories for the children were calculated in part from the menus of six boarding church schools. Nutrient calculations of daily intake were based upon food composition tables and some actual analyses of Tarahumara foods. The protein intake was ample, at 87 g, and generously met the FAO/WHO recommendations for daily intake of essential amino acids. Fat contributed only 12% of total calories, its composition being 2% saturated and 5% polyunsaturated with a P/S ratio of 2. The mean dietary cholesterol intake was very low, less than 100 mg/day, and the plant sterol intake was high, over 400 mg/day. Carbohydrate comprised 75 to 80% of total calories, mostly from starch. Only 6% of total calories were derived from simple sugars. The crude fiber intake was high, 18 to 21 g/day. Salt consumption was moderately low, 5 to 8 g/day. The daily intakes of calcium, iron, vitamin A, ascorbic acid, thiamin niacin, riboflavin, and vitamin B6 exceeded or approximated the FAO/WHO recommendations. Thus, the simple diet of the Tarahumara Indians, composed primarily of beans and corn, provided a high intake of complex carbohydrate and was low in fat and cholesterol. Their diet was found to be generally of high nutritional quality and would, by all criteria, be considered antiatherogenic.

Adolescent↗